title: Alpinetin inhibits LPS-induced inflammatory mediator response by activating PPAR-γ in THP-1-derived macrophages.
abstract: Alpinetin, a novel plant flavonoid derived from Alpinia katsumadai Hayata, has been reported to have anti-inflammatory properties. However, the anti-inflammatory mechanism of alpinetin has not been fully elucidated. The purpose of this study was to investigate the anti-inflammatory mechanism of alpinetin in modifying lipopolysaccharide (LPS)-induced signaling pathways in human THP-1 macrophages. The cells were stimulated with LPS in the presence or absence of alpinetin. The pro-inflammatory cytokines were evaluated by ELISA and qRT-PCR. Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and PPAR-γ were determined by Western blotting. The results showed that alpinetin inhibited TNF-α, IL-6 and IL-1β expression in LPS-stimulated human THP-1 macrophages in a dose-dependent manner. Western blot analysis showed that alpinetin suppressed LPS-induced NF-κB activation, IκBα degradation, phosphorylation of ERK, JNK and P38. Furthermore, alpinetin could significantly down-regulated the expression of TLR4 stimulating by LPS. We also found that alpinetin could activate PPAR-γ and the anti-inflammatory effects of alpinetin can be reversed by GW9662, a specific antagonist for PPAR-γ. These results suggest that alpinetin activates PPAR-γ, thereby attenuating TLR4 expression and TLR4 mediated NF-κB and MAPK activation and the release of pro-inflammatory cytokines. These findings suggest that alpinetin may be a therapeutic agent against inflammatory diseases.
authors.affiliation: Department of Senile Disease, the Third Xiang Ya Hospital, Central South University, Tongzipo Road no.138, Changsha, Hunan 410013, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Qiuyun
authors.initials: Q
authors.lastname: Tu
authors.forename: Yingquan
authors.initials: Y
authors.lastname: Luo
authors.forename: Ruoting
authors.initials: R
authors.lastname: Ma
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D044950:Flavanones / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D044950:Flavanones; D008024:Ligands; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C436748:alpinetin; D020928:Mitogen-Activated Protein Kinases
keywords: Alpinetin; Cytokine; LPS; MAPK; NF-κB; PPAR-γ; TLR4